T Cell Receptor Signaling

Antigen-specific activation of T lymphocytes via TCR-MHC interaction.

Overview

TCR signaling begins when the TCR recognizes peptide-MHC complexes. This triggers phosphorylation of ITAMs on CD3 chains by Lck, recruitment and activation of ZAP-70, and downstream activation of PLCγ1, RAS-MAPK, and PI3K-AKT pathways. Key transcription factors activated include NFAT, NF-κB, and AP-1.

Cellular Location

T cell membrane → cytoplasm → nucleus

Clinical Significance

Basis of adaptive immunity; target of immunosuppressants (cyclosporine); CAR-T therapy engineers this pathway for cancer treatment.

Key Molecules

TCR-CD3 complex MHC-peptide CD4/CD8 Lck ZAP-70 LAT SLP-76 NFAT AP-1 IL-2

Key Enzymes

Lck (Src kinase)ZAP-70 PLCγ1 Calcineurin PKCθ PI3K

Related Pathways

NF-κB Pathway

Master regulator of inflammation, immunity, and cell survival.

MAPK/ERK Pathway

RAS–RAF–MEK–ERK cascade transducing growth factor signals to the nucleus.

PI3K/AKT/mTOR Pathway

Regulates cell survival, growth, and metabolism via phosphoinositide signaling.